Analysis Of Driver Gene Mutation In Non-small Cell Lung Cancer And Its Correlation With Clinical Features

Objective:By collecting the Next-generation sequencing results of genes mutations of NSCLC,analyzing the mutation sites and mutation types of driver genes,and investigating the correlation between these driver genes and clinical characters of NSCLC,to deepen the understanding of the molecular mechanism of lung cancer.It also provides theoretical basis for the individualized treatment in NSCLC.Methods:1.The 72 cases of NSCLC patients were collected from the ChinaJapan Union Hospital of Jilin University from January 2015 to December2017,which confirmed by histopathology and driver genes were detected by Ion Torrent platform.Recorded clinical data of all patients,including:(1)patients' gender,age,smoking history and so on;(2)specimen origin,pathological type and degree of differentiation;(3)TNM staging of lung cancer(TNM staging of the 7th version of UICC);(4)Most of the patients did not have adequate treatment data,no statistical treatment and prognosis.2.Analyzing the 72 cases of NSCLC patients' results of gene mutation detected by Ion Torrent platform(11 patients examined 62 genes,and 61 patients tested 25 genes,the former 62 genes contain the latter 25 genes.),including mutated genes,locus of mutation,type of mutation,number of mutations,and so on.3.Using percentage expresses gene mutation rate(keeping two decimal places).By chi-square test in SPSS 22.0 statistical analysis software to investigate the correlation between driver genes and clinical characters of NSCLC.Inspection level =0.05.Result:1.29 genes were detected by Ion Torrent in 72 cases of NSCLC,and the proportion of mutations in samples were: 52 cases of EGFR mutation,accounted for 34.72%,24 cases of TP53 mutation,accounted for 33.33%,KRAS 29.17%,PIK3 CA 13.89%,NOTCH1 6.94%.And ERBB2(HER2)?CREBBP ? PTEN ? FGFR1 and TSC1 gene mutations were all 4 cases,accounted for 5.56%.Other mutant genes were CCND1,ERBB4,FPR1,FGFR3,COL22A1,FLT3,ALK,NOTCH3,DDR2,ROS1,MET,BRAF,NRAS,MAP2K1,AKT1,FMN2,RET,KDR.2.In the 72 samples,specific mutation information was statistically analyzed for the common driver gene(mutation frequency > 10%):2.1 25 cases of EGFR gene mutations(25/72,34.72%),including 2cases located at exons 18(2/25,8%),14 cases located at exons 19(14/25,56%),3 cases located at exons 20(3/25,12%),9 cases located at exons 21(9/25,36%).There were 4 cases have two mutations in the EGFR gene.Its mutated type is mainly missense mutation and deletion mutation.2.2 Among all the samples,there were 24 cases of TP53 gene mutations(33.33%),of which 4 exon and 10 exon mutation rate is 4.17%(1/24).Themutation rate of exon 5 is 37.5%(9/24).exon 6 12.5%(3/24),exon 733.33%(8/24),exon 8 25%(6/24).The mutation is mainly a missense mutation.2.3 there were 17 cases detected with KRAS gene mutation(17/72,33.33%),both of them were missense mutation,there were 8 unique mutation sites.14 case located at exons 2(14/17,82.35%),2 case located at exons 3(2/17,11.76%),1 case located at exons 4(1/17,5.88%).2.4 there were 10 cases detected with PIK3 CA gene mutation(10/72,13.89%).4 case located at exons 9(4/10,40%),3 case located at exons13(3/10,30%),1 case located at exons 4(1/10,10%).3.Analyzing the correlation between driver genes and Clinical features:3.1 EFGR mutation rate correlate with gender,pathological type,smoking history,degree of differentiation(P<0.05),showing that the EFGR mutation rate is higher in patients of women(P = 0.008),adenocarcinoma(P= 0.036),and non-smokers(P = 0.027)than others,while there is no obvious correlation with other characters(P > 0.05).3.2 TP53 mutation rate correlate with age,pathological type,smoking history,lymph node metastasis in NSCLC with statistical significance(P<0.05),showing that the TP53 mutation rate is higher in patients of older than 60.(P = 0.017),adenocarcinoma(P = 0.045),smokers(P = 0.045)and lymph node metastasis(P = 0.019)than others,while there is no obvious correlation with other characters(P > 0.05).3.3 KRAS mutation rate correlate with smoking history in NSCLC with statistical significance(P<0.05),showing that the TP53 mutation rate is higher in patients of older than smokers(P = 0.003),while there is no obvious correlation with other characters(P > 0.05).4.In the samples detected by Ion Torrent,the variant allele frequency(VAF)was less than 0.24%.The mutation of VAF less than 5% was 7.32%.Conclusions:1.The most common driver gene mutations in non-small cell lung cancer in China were EGFR,TP53,KRAS and PIK3 CA genes.The EGFR(34.72%)mutations mostly locate on exon 19,account for more than 50%;TP53 gene mutation sites were widely distributed;The KRAS mutations mostly locate on exon 2;Mutations in the PIK3 CA gene were all missense mutation.2.Women with adenocarcinoma and non-smoking are more likely to have EGFR mutations.Elderly,squamous cell carcinoma,smoking and lymph node metastasis are at high risk of TP53 gene mutation.Patients with smoking history were more likely to have mutations in the KRAS gene.3.Ion Torrent platform shows high sensitivity.